Zhang Y, Axiak-Bechtel S, Friedman Cowan C, Amorim J, Tsuruta K, DeClue A E
Comparative Internal Medicine Laboratory, Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65211, USA.
Comparative Oncology Laboratory, Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65211, USA.
Vet Comp Oncol. 2017 Sep;15(3):968-979. doi: 10.1111/vco.12236. Epub 2016 Apr 21.
The objective of this in vitro study was to evaluate the immunomodulatory effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on polymorphonuclear cell (PMN) function in dogs with cancer. PMNs were harvested from dogs with naturally developing cancer as a pre-clinical model to evaluate the immunomodulatory effects of rhGM-CSF on PMN phagocytic and cytotoxic functions, cytokine production and receptor expression. Some aspects of cancer-related PMN dysfunction in dogs with cancer were restored following incubation with rhGM-CSF including PMN phagocytosis, respiratory burst and LPS-induced TNF-α production. In addition, rhGM-CSF increased surface HLA-DR expression on the PMNs of dogs with cancer. These data suggests that dysfunction of innate immune response in dogs with cancer may be improved by rhGM-CSF. The results of this study provided a pathophysiologic rationale for the initiation of clinical trials to continue evaluating rhGM-CSF as an immunomodulatory therapy in dogs with cancer.
本体外研究的目的是评估重组人粒细胞巨噬细胞集落刺激因子（rhGM-CSF）对患癌犬多形核细胞（PMN）功能的免疫调节作用。从自然患癌犬获取PMN作为临床前模型，以评估rhGM-CSF对PMN吞噬和细胞毒性功能、细胞因子产生及受体表达的免疫调节作用。患癌犬与rhGM-CSF孵育后，癌症相关的PMN功能障碍的某些方面得以恢复，包括PMN吞噬作用、呼吸爆发和脂多糖诱导的TNF-α产生。此外，rhGM-CSF增加了患癌犬PMN表面HLA-DR的表达。这些数据表明，rhGM-CSF可能改善患癌犬先天免疫反应的功能障碍。本研究结果为启动临床试验以继续评估rhGM-CSF作为患癌犬免疫调节疗法提供了病理生理学依据。
